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Pneumococcal pneumonia in children Authors: Elaine I Tuomanen, MD Sheldon L Kaplan, MD Section Editor: Morven S Edwards, MD Deputy Editor: Mary M Torchia, MD Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2016. | This topic last updated: Oct 16, 2015. INTRODUCTION — Pneumococcus (Streptococcus pneumoniae) is a common cause of invasive bacterial infection in children and a frequent cause of community-acquired pneumonia (CAP) [1,2]. Intermediate or high-level resistance to penicillin has become a significant problem. Children, particularly those in child care facilities and those receiving frequent courses of antibiotics, appear to be important carriers of resistant strains [3-5]. The clinical features, diagnosis, and treatment of pneumococcal pneumonia will be reviewed here. An overview of the clinical features and diagnosis of CAP in children and the microbiology, pathogenesis, and epidemiology of S. pneumoniae are discussed separately. (See "Community-acquired pneumonia in children: Clinical features and diagnosis" and "Microbiology and pathogenesis of Streptococcus pneumoniae".) PATHOGENESIS — The pneumococcus is acquired by aerosol or inhalation, leading to colonization of the nasopharynx; pneumococci are carried asymptomatically in approximately 50 percent of individuals at any point in time [6]. In children, the incidence of pneumococcal carriage may be as high as 60 percent, even after immunization with the pneumococcal conjugate vaccine [7-9] (see "Microbiology and pathogenesis of Streptococcus pneumoniae", section on 'Pathogenesis'). Antibiotic-resistant strains are increasingly common [10]. (See "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and "Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole" and"Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamines, and ketolides".) Invasive disease most commonly occurs upon acquisition of a new serotype, typically after an incubation period of one to three days. The incidence of disease increases strongly in association with a viral illness, such as influenza, parainfluenza, respiratory syncytial virus, adenovirus, or human metapneumovirus [11-14]. In a case-control study, upper respiratory infections with viruses such as influenza and parainfluenza correlated with acquisition of new serotypes of pneumococci in children [15]. This association is believed to be related to increased expression of receptors for pneumococcal attachment on virally activated respiratory epithelial cells [16]. In addition, viral neuraminidases cleave sialic acid from host cell glycoconjugates, and the resulting free sugar is used as a nutrient to increase the growth and density of pneumococci in the nasopharynx [17]. This adds another dimension to the synergy between viruses and pneumococci in the pathogenesis of pneumonia. Pneumococci are presumably aerosolized from the nasopharynx to the alveolus, where they enter alveolar type II cells. This invasive process involves bacterial binding to the receptor for platelet activating factor (PAF), a key pulmonary chemokine [18]. The binding occurs via choline, a chemical constituent shared between the surface of the bacteria and PAF. Choline is present on the surfaces of many pulmonary pathogens, suggesting a common mechanism for pulmonary infection [19]. The innate host C-reactive protein binds to choline and opsonizes pathogens that pass from the lungs into the bloodstream. Thus, although choline is useful in the organism's binding to the lung, it is detrimental to the organism in the bloodstream. (See "Microbiology and pathogenesis of Streptococcus pneumoniae", section on 'Pathogenesis'.) The pneumonic lesion progresses as pneumococci multiply in the alveolus and invade the alveolar epithelium. Pneumococci pass from alveolus to alveolus through the pores of Cohn, thereby creating inflammation and consolidation strictly along lobar compartments. The center of the spreading lesion shows more advanced inflammation than do the edges. The evolution of lung consolidation is as follows [20]: ●Newly involved regions demonstrate engorgement of alveolar capillaries with frothy, serous, blood-tinged fluid in the alveolar spaces. This lesion can be recapitulated by instillation of heat-killed pneumococci into the lung and, therefore, may result from host response to the pneumococcal cell wall [21]. ●Engorgement of alveolar capillaries rapidly progresses to red hepatization, characterized by a dry, granular, dark red lung surface and alveoli filled with copious, clotted inflammatory exudate. A distinctive feature of the exudate is its "freshness" in that erythrocytes and leukocytes are intact, and a fibrin network extends from one alveolus into the next through the pores of Cohn. Pneumococci are intact and alive. Bronchoalveolar lavage fluid contains large amounts of tumor necrosis factor, interleukin-6, and nitric oxide reflective of strong recruitment of leukocytes to the infected focus [22]. However, little tissue destruction or necrosis occurs during this process, perhaps explaining why the patient and lung architecture may recover fully from these lesions. ●As red hepatization progresses over two to three days, leukocytes pack into the alveoli, erythrocytes are lysed, and epithelial cells degenerate, leading to grey hepatization. Dying pneumococci release the poreforming toxin pneumolysin, which contributes to this damage. ●In the presence of antibody, pneumococci are opsonized and then phagocytosed by leukocytes and begin to be cleared. Consolidation remains prominent after defervescence. An abrupt disappearance of fever, termed "crisis," is particularly common in children. Resolution results in a jelly-like consistency to the lung with a slimy, yellowish exudate. The involvement of mononuclear cells in the exudate is characteristic of this stage. Absorption of the exudate is remarkably efficient, with little organization or permanent scarring. EPIDEMIOLOGY Burden of disease — Pneumonia is the single most common disease causing death in children worldwide [23]. Community-acquired pneumonia (CAP) can be caused by a variety of bacterial and viral pathogens, and the predominant pathogen varies depending on age. Overall, S. pneumoniae is the most common cause of CAP, although in many cases an organism cannot be isolated. The burden of pneumococcal pneumonia in children declined after the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced with the 13-valent pneumococcal conjugate (PCV13) vaccine in 2010 [24]. (See "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'Community-acquired pneumonia'.) Serotypes — The pneumococcal serotypes isolated from children with pneumococcal pneumonia have changed since the addition of PCV7 (table 1) to the routine childhood immunization schedule in the United States. In the prePCV7 era, serotypes 6B, 14, and 19F were the most frequently isolated in both complicated and uncomplicated disease [25,26]. Following introduction of PCV7 in 2000, serotypes not included in PCV7, including serotypes 1, 3, 5, 7F, 12, and 19A, were more frequently isolated, particularly from children with complicated pneumonia [27-32]. PCV13, which contains all of these serotypes except 12, replaced PCV7 in 2010. During 2011 surveillance for invasive pneumococcal infections at eight children's hospitals in the United States, serotypes 19A and 7F remained the most common serotypes isolated from children hospitalized with pneumonia [33]. In another study, serotype 3 was isolated from pleural fluid specimens in 15 of 20 children with pneumococcal empyema, one-third of whom had received PCV13 [34]. (See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section on '13-valent vaccine' and 'Effusion/empyema' below.) Risk factors — Risk factors for invasive pneumococcal disease are listed in the table (table 2). Antibiotic resistance — Resistance of S. pneumoniae to multiple antibiotics is an increasingly important clinical problem. A discussion of pneumococcal drug resistance is presented separately. (See "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and "Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamines, and ketolides" and "Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole".) CLINICAL FEATURES Transmission and incubation period — S. pneumoniae is transmitted from person to person through contact with respiratory droplets [2]. The period of communicability is not known but is probably less than 24 hours after initiation of appropriate antimicrobial therapy. The incubation period depends upon the type of infection, but may be as short as one to three days [2]. Clinical manifestations — Pneumococcal pneumonia is the paradigm of classic lobar bacterial pneumonia [20]. The most common clinical signs and symptoms are fever, nonproductive cough, tachypnea, and decreased breath sounds over the affected area. Auscultatory findings of crepitant rales (crackles) and tubular breath sounds are highly localized to the involved segment or lobe. These findings may disappear at the height of consolidation and reappear on resolution (redux crepitus). (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clues to etiology'.) In a retrospective review of 254 children and young adults (age <1 month to 26 years) with pneumococcal pneumonia (confirmed by blood or pleural fluid culture), the most common signs and symptoms and their approximate frequencies are listed below [35]: ●Fever – 90 percent (mean duration three days before diagnosis) ●Cough – 70 percent; productive cough: 10 percent ●Tachypnea – 50 percent ●Malaise/lethargy – 45 percent ●Emesis – 43 percent ●Hypoxemia (oxygen saturation ≤95 percent) – 50 percent ●Decreased breath sounds – 55 percent ●Crackles – 40 percent ●Retractions – 30 percent ●Grunting – 25 percent ●Abdominal pain – 20 percent ●Chest pain – 10 percent Radiographic features — Pneumococci can cause lobar or bronchopneumonia. S. pneumoniae is the most common bacterial cause of sphere-shaped consolidation (ie, "round pneumonia"). However, this finding is not pathognomonic because round pneumonia can also be caused by other streptococci, Haemophilus influenzae, staphylococci, Mycoplasma pneumoniae, lung abscess, and noninfectious conditions. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Etiologic clues'.) Complications — In ambulatory children, pneumococcal pneumonia characteristically is uncomplicated, with complete recovery of normal pulmonary architecture and function. However, complications occur in approximately 40 to 50 percent of children hospitalized with pneumococcal pneumonia [26,36]. Potential complications include [26,3639]: ●Pleural effusion ●Empyema ●Lung abscess ●Necrotizing pneumonia (particularly with serotype 3 and serogroup 19) (image 1) ●Atelectasis ●Pneumatocele ●Pneumothorax In addition, pneumococcal pneumonia has been associated with hemolytic uremic syndrome [40,41]. (See"Overview of hemolytic uremic syndrome in children", section on 'Streptococcus pneumoniae'.) In a review of 111 children (0 to 16 years) hospitalized with confirmed pneumococcal pneumonia during 1986 to 1997, complicated pneumonia occurred in 39 percent [36]. More than one complication occurred in 60 percent of patients; the distribution of complications was as follows: ●Pleural effusion – 83 percent ●Empyema – 52 percent ●Atelectasis – 26 percent ●Pneumatocele – 19 percent ●Pneumothorax – 10 percent Complications correlated with weight ≤10th percentile for age, respiratory distress, anemia, and white blood cell count <15,000/microL at the time of admission, but not with pneumococcal susceptibility to penicillin, chronic illness, or comorbid conditions. Patients with complications had increased length of stay (13 versus 5 days) and duration of fever (9 versus 2 days) compared with those without complications. Advanced testing for viruses in children with bacterial pneumonia has revealed frequent coinfection. Although the clinical significance of these viruses remains unclear, coinfection can be associated with a complicated course [4244]. Pneumococcal parapneumonic effusion/empyema is discussed briefly below and in greater detail separately. (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children"and "Management and prognosis of parapneumonic effusion and empyema in children".) The other complications are discussed separately. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Complications'.) Effusion/empyema — Data from the United States Pediatric Multicenter Pneumococcal Surveillance Group indicate that the frequency of pneumococcal pneumonia complicated by loculated pleural effusion or empyema increased in the period before the recommendation for universal immunization of infants with the pneumococcal conjugate vaccine in 2000 [26]. Between 1993 and 2000, 368 children were hospitalized with culture-confirmed pneumococcal pneumonia; 36 percent met criteria for pneumonia complicated by loculated pleural effusion or empyema. (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Epidemiology' and "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Clinical presentation'.) The incidence of pneumococcal parapneumonic empyema continued to increase after the recommendation for routine immunization of infants in the United States with the pneumococcal conjugate vaccine [27,45,46]. In Utah's Intermountain Healthcare system, pneumococcal parapneumonic effusion accounted for 17.5 percent of cases of invasive pneumococcal disease in the period before routine vaccination (1996 to 2000) and 32 percent of cases of invasive pneumococcal disease after routine vaccination. In both periods, serotype 1 was the most common cause of pneumococcal parapneumonic empyema; in the period after routine vaccination, serogroups 3, 7F, and 19A also were prevalent [27]. (See 'Serotypes' above.) Parapneumonic effusions caused by strains intermediate or resistant to penicillin are associated with younger age than those caused by susceptible organisms (two versus eight years). Parapneumonic effusions caused by strains intermediate or resistant to penicillin usually are accompanied by bacteremia, but do not result in a poorer outcome than susceptible strains [26,47,48]. The clinical features, diagnosis, and management of parapneumonic effusions are discussed separately. (See"Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Clinical presentation' and "Management and prognosis of parapneumonic effusion and empyema in children", section on 'Overview'.) DIAGNOSIS — The history, physical findings, and finding of an infiltrate on chest radiograph usually establish the diagnosis of pneumonia. Although lobar consolidation is suggestive of bacterial pneumonia, radiologists cannot reliably differentiate bacterial from nonbacterial pneumonia on the basis of the radiographic appearance [49]. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Radiologic evaluation'.) Blood or pleural fluid cultures — Culture of the blood or pleural fluid is the most important method for identifying the etiology of pneumonia. Among normal children hospitalized with pneumonia, approximately 10 to 15 percent have positive cultures, primarily for S. pneumoniae. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Cultures'.) Antigen detection — Antigen detection by latex agglutination for pneumococcal polysaccharide in urine is not sensitive enough to be useful. However, in children with parapneumonic effusion or empyema who were treated with antibiotics before pleural fluid was obtained, detection of pneumococcal antigen in pleural fluid can confirm the diagnosis [50]. (See "Epidemiology; clinical presentation; and evaluation of parapneumonic effusion and empyema in children", section on 'Microbial analysis'.) Polymerase chain reaction — Polymerase chain reaction (PCR) tests for pneumococcus in sputum and blood have been developed [51,52]. However, the sensitivity and specificity of these tests in children have not been conclusively established, and their routine use is not recommended [53,54]. Sputum Gram stain and culture — Among outpatients, pneumococcal pneumonia must be differentiated from other causes of community-acquired pneumonia (CAP). However, an etiologic agent is identified in less than one-half of cases [1]. Two problems make it difficult to identify the inciting organism: most children are unable to produce a sputum specimen, and approximately 25 percent of patients have received antibiotics before presentation [35]. For these and other reasons, sputum Gram stain and culture are of little value in children, and most patients with CAP are treated empirically. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Laboratory evaluation' and "Community-acquired pneumonia in children: Outpatient treatment", section on 'Empiric therapy'.) If a sputum sample is available, a Gram stain should be performed, and the specimen should be analyzed for the presence of polymorphonuclear leukocytes (PMN), epithelial cells, and bacteria. ●A specimen that has more than 25 PMN and less than 10 epithelial cells per low power field (x100) represents a purulent specimen. Individual microbiology laboratories may use slightly different criteria. However, all define purulence based upon an increased number of PMN and a low (or absent) number of epithelial cells. ●The finding of a predominant organism (for example, gram-positive diplococci) may identify the cause of the pneumonia (picture 1). When gram-positive, lancet-shaped diplococci are the predominant flora or there are more than 10 gram-positive, lancet-shaped diplococci per oil immersion field (x1000), the sensitivity and specificity for pneumococci identified by quellung reaction or culture are 62 percent and 85 percent, respectively [55]. TREATMENT — The treatment recommendations below are consistent with those in the 2011 clinical practice guidelines of the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America [56]. Supportive care — Supportive care for children with pneumonia is discussed separately. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Supportive care' and "Pneumonia in children: Inpatient treatment", section on 'Supportive care'.) Empiric therapy — Most patients with community-acquired pneumonia (CAP) are treated empirically. Whether or not to include agents with activity against S. pneumoniae depends upon the age of the child, epidemiologic and clinical information, and laboratory and imaging studies if such studies were obtained. Empiric therapy for S. pneumoniae is generally included for children who require inpatient treatment for CAP and children who have clinical findings compatible with bacterial pneumonia (eg, lobar or round consolidation on radiograph, leukocytosis, elevated C-reactive protein, complications). Empiric therapy for CAP is discussed separately. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Empiric therapy' and "Pneumonia in children: Inpatient treatment", section on 'Empiric therapy'.) Children who are not critically ill can be treated with oral antibiotics. Some patients may benefit from initial parenteral antibiotic therapy. In a retrospective study, children with bacteremic pneumococcal pneumonia who received initial parenteral antibiotic followed by oral therapy were less likely to be admitted to the hospital (0 versus 24 percent) and more likely to have their parents report improvement at follow-up (95 versus 67 percent) than were those who received oral treatment alone [57]. Children who appear toxic or have evidence of complications, such as empyema, require intravenous therapy. For children with serious allergic reactions to beta-lactam antibiotics, initial empiric therapy should includevancomycin or clindamycin. (See "Pneumonia in children: Inpatient treatment", section on 'Empiric therapy' and"Management and prognosis of parapneumonic effusion and empyema in children", section on 'Antibiotic therapy'.) Specific therapy — When there is a positive culture for S. pneumoniae, the antibiotic susceptibility pattern (table 3) should guide therapy. Parenteral and oral regimens for anti-pneumococcal agents are provided in the table (table 4). Penicillin-susceptible strains — Penicillin or ampicillin is the drug of choice for parenteral treatment of pneumococcal pneumonia caused by isolates with penicillin MICs ≤2 mcg/mL (table 3 and table 4) [56,58-63]. Penicillin and ampicillin are less expensive than alternative agents for penicillin-susceptible strains. Alternative parenteral therapies (if the isolate is susceptible) include cefotaxime, ceftriaxone, clindamycin, vancomycin, andlevofloxacin if the isolate is susceptible. Clindamycin is an alternative for patients with severe hypersensitivity to beta-lactam antibiotics. Ceftriaxone is preferred for outpatient parenteral therapy. Vancomycin may be warranted for children with severe hypersensitivity to beta-lactam antibiotics and an isolate resistant to clindamycin. Oral amoxicillin is the drug of choice for oral treatment of pneumococcal pneumonia caused by isolates with penicillin MICs ≤2 mcg/mL. Alternative oral therapies (if the isolate is susceptible) include cefpodoxime,cefprozil, cefuroxime, and levofloxacin (table 4). Clindamycin is an alternative for patients with severe hypersensitivity to beta-lactam antibiotics if the isolate is susceptible (table 3). Intermediate and resistant strains — Ceftriaxone or cefotaxime are preferred for parenteral treatment for pneumococcal pneumonia caused by isolates with penicillin MICs >2 mcg/mL (table 3 and table 4). Vancomycin,levofloxacin, linezolid, and clindamycin are alternatives. Nonsusceptibility to ceftriaxone or cefotaxime appears to be decreasing with the decreasing frequency of serotype 19A (which is included in the 13valent pneumococcal conjugate vaccine, licensed in 2010) [64,65]. Oral levofloxacin or linezolid are the drugs of choice for oral treatment of pneumococcal pneumonia caused by isolates with penicillin MICs >2 mcg/mL. Clindamycin is an alternative parenteral or oral therapy (if the isolate is susceptible). Clones of the pneumococcal serotype 19A in particular may be resistant to penicillin, macrolides, clindamycin, and trimethoprim-sulfamethoxazole. Such multidrug-resistant isolates may require treatment with vancomycin,linezolid, or levofloxacin [66-68]. Duration of therapy — Therapy generally is continued for a total period of five to seven days for uncomplicated pneumonia or until the patient is afebrile for five days in more severe cases. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Duration' and "Pneumonia in children: Inpatient treatment", section on 'Duration of treatment'.) Empyema — The treatment of empyema is discussed separately. (See "Management and prognosis of parapneumonic effusion and empyema in children".) RESPONSE TO THERAPY — Children with pneumonia who are appropriately treated should show signs of improvement within 24 to 48 hours. Failure to improve as anticipated may indicate: ●Alternative or coincident diagnosis (eg, foreign body aspiration) (see "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Differential diagnosis') ●Ineffective antibiotic coverage (eg, resistant organism) (see "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and "Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamines, and ketolides" and "Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-sulfamethoxazole") ●Development of complications (see 'Complications' above) These possibilities are discussed separately. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Treatment failure' and "Pneumonia in children: Inpatient treatment", section on 'Treatment failure'.) FOLLOW-UP — The clinical and radiographic follow-up for children with pneumonia are discussed separately. (See "Pneumonia in children: Inpatient treatment", section on 'Follow-up' and "Community-acquired pneumonia in children: Outpatient treatment", section on 'Follow-up'.) OUTCOME — Most otherwise healthy children with pneumococcal pneumonia, even complicated pneumococcal pneumonia, recover without sequelae. The Centers for Disease Control and Prevention (CDC) examined pneumococcal pneumonia in 5837 patients from nine geographic areas in the United States; 7 percent were younger than 18 years old [69]. The case fatality rates for pneumococcal pneumonia for children in the United States from 1995 to 1997 (not adjusted for comorbid conditions) were estimated to be 4 percent in children younger than two years and 2 percent in children 2 to 17 years [69]. PREVENTION Infection control — Standard isolation precautions are recommended for children with pneumococcal pneumonia [2]. (See "General principles of infection control", section on 'Standard precautions'.) Active immunization — Immunization with the pneumococcal conjugate vaccine (PCV) is recommended for all infants in the United States. The efficacy of PCV in preventing pneumonia is discussed separately. (See"Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children", section on 'Indications'.) Children who are at increased risk of invasive pneumococcal disease (table 2) also should receive thepneumococcal polysaccharide vaccine beginning at two years of age; the pneumococcal polysaccharide vaccine should be administered at least eight weeks after PCV. (See "Pneumococcal (Streptococcus pneumoniae) polysaccharide vaccines in children", section on 'Indications'.) INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) ●Basics topics (see "Patient education: Pneumonia in children (The Basics)") SUMMARY AND RECOMMENDATIONS ●Streptococcus pneumoniae is the most common cause of bacterial pneumonia. However, in certain age groups, other causes of pneumonia predominate. (See 'Burden of disease' above and "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.) ●The most common clinical manifestations of pneumococcal pneumonia are fever, non-productive cough, tachypnea, and decreased breath sounds over the affected area. Auscultatory findings of crepitant rales (crackles) and tubular breath sounds are highly localized to the involved segment or lobe. (See 'Clinical manifestations' above.) ●Complications, which are present in 40 to 50 percent of children hospitalized with pneumococcal pneumonia, include pleural effusion, empyema, lung abscess, necrotizing pneumonia, atelectasis, pneumatocele, and pneumothorax. (See 'Complications' above.) ●History, examination, and radiographic findings usually establish the diagnosis of pneumonia. Although lobar consolidation is suggestive of bacterial pneumonia, radiographic features cannot reliably differentiate bacterial from nonbacterial pneumonia. Specific diagnosis of pneumococcal pneumonia in children is usually made through culture of the blood or pleural fluid. (See 'Diagnosis' above.) ●Most patients with community-acquired pneumonia are treated empirically. If S. pneumoniae is a consideration, empiric therapy generally includes a beta-lactam antibiotic (ie, penicillin or cephalosporin). Children who appear toxic or have evidence of complications require intravenous therapy. Children who are not critically ill can be treated orally. (See 'Empiric therapy' above.) ●When there is a positive culture for S. pneumoniae, the antibiotic susceptibility pattern should guide therapy (table 3). (See 'Specific therapy' above.) •We suggest penicillin or ampicillin as the parenteral drug of choice and amoxicillin as the oral drug of choice for pneumococcal pneumonia caused by isolates with penicillin MICs ≤2 mcg/mL (Grade 2B). Alternative parenteral agents include cefotaxime, ceftriaxone, clindamycin, vancomycin, or levofloxacinif the isolate is susceptible. Alternative oral therapies include cefpodoxime, cefprozil, cefuroxime, levofloxacin. Doses are provided in the table (table 4). •We suggest ceftriaxone or cefotaxime as the preferred parenteral treatment and oral levofloxacin orlinezolid as the preferred oral treatment for pneumococcal isolates with penicillin MICs >2 mcg/mL(table 4) (Grade 2C). Vancomycin, levofloxacin, linezolid, and clindamycin (if the isolate is susceptible) are alternatives. ●Therapy generally is continued for five to seven days for uncomplicated disease or until the patient is afebrile for five days in more severe cases. (See 'Duration of therapy' above.) ●Most otherwise-healthy children with pneumococcal pneumonia, even complicated pneumococcal pneumonia, recover without sequelae. The case fatality rates for pneumococcal pneumonia for children in the United States are estimated to be 4 percent in children younger than two years and 2 percent in children 2 to 17 years. (See 'Outcome' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. 2. 3. 4. 5. 6. Wubbel L, Muniz L, Ahmed A, et al. Etiology and treatment of community-acquired pneumonia in ambulatory children. Pediatr Infect Dis J 1999; 18:98. American Academy of Pediatrics. Pneumococcal infections. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.626. Thornsberry C, Ogilvie PT, Holley HP Jr, Sahm DF. Survey of susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates to 26 antimicrobial agents: a prospective U.S. study. Antimicrob Agents Chemother 1999; 43:2612. Sisson BA, Buck G, Franco SM, et al. Penicillin minimum inhibitory concentration drift in identical sequential Streptococcus pneumoniae isolates from colonized healthy infants. Clin Infect Dis 2000; 30:191. Raymond J, Le Thomas I, Moulin F, et al. Sequential colonization by Streptococcus pneumoniae of healthy children living in an orphanage. J Infect Dis 2000; 181:1983. Austrian R. Some aspects of the pneumococcal carrier state. J Antimicrob Chemother 1986; 18 Suppl A:35. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. Millar EV, O'Brien KL, Watt JP, et al. Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population. Clin Infect Dis 2006; 43:8. Huang SS, Platt R, Rifas-Shiman SL, et al. Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. Pediatrics 2005; 116:e408. Park SY, Moore MR, Bruden DL, et al. Impact of conjugate vaccine on transmission of antimicrobialresistant Streptococcus pneumoniae among Alaskan children. Pediatr Infect Dis J 2008; 27:335. Overturf GD. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics 2000; 106:367. Madhi SA, Klugman KP, Vaccine Trialist Group. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004; 10:811. Madhi SA, Ludewick H, Kuwanda L, et al. Pneumococcal coinfection with human metapneumovirus. J Infect Dis 2006; 193:1236. Ampofo K, Bender J, Sheng X, et al. Seasonal invasive pneumococcal disease in children: role of preceding respiratory viral infection. Pediatrics 2008; 122:229. O'Brien KL, Walters MI, Sellman J, et al. Severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection. Clin Infect Dis 2000; 30:784. Grijalva CG, Griffin MR, Edwards KM, et al. The role of influenza and parainfluenza infections in nasopharyngeal pneumococcal acquisition among young children. Clin Infect Dis 2014; 58:1369. Tuomanen EI, Austrian R, Masure HR. Pathogenesis of pneumococcal infection. N Engl J Med 1995; 332:1280. Siegel SJ, Roche AM, Weiser JN. Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source. Cell Host Microbe 2014; 16:55. Cundell DR, Gerard NP, Gerard C, et al. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 1995; 377:435. Weiser JN, Pan N, McGowan KL, et al. Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 1998; 187:631. Heffron R. Pneumonia. Commonwealth Fund, New York 1939. Tuomanen E, Rich R, Zak O. Induction of pulmonary inflammation by components of the pneumococcal cell surface. Am Rev Respir Dis 1987; 135:869. Bergeron Y, Ouellet N, Deslauriers AM, et al. Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice. Infect Immun 1998; 66:912. UNICEF. Pneumonia: The forgotten killer of children. UNICEF/WHO 2006. www.unicef.org/publications/index_35626.html (Accessed on June 20, 2012). Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis 2015; 15:301. Kaplan SL, Mason EO Jr, Wald E, et al. Six year multicenter surveillance of invasive pneumococcal infections in children. Pediatr Infect Dis J 2002; 21:141. Tan TQ, Mason EO Jr, Wald ER, et al. Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae. Pediatrics 2002; 110:1. Byington CL, Hulten KG, Ampofo K, et al. Molecular epidemiology of pediatric pneumococcal empyema from 2001 to 2007 in Utah. J Clin Microbiol 2010; 48:520. Schutze GE, Tucker NC, Mason EO Jr. Impact of the conjugate pneumococcal vaccine in arkansas. Pediatr Infect Dis J 2004; 23:1125. Byington CL, Samore MH, Stoddard GJ, et al. Temporal trends of invasive disease due to Streptococcus pneumoniae among children in the intermountain west: emergence of nonvaccine serogroups. Clin Infect Dis 2005; 41:21. Chibuk TK, Robinson JL, Hartfield DS. Pediatric complicated pneumonia and pneumococcal serotype replacement: trends in hospitalized children pre and post introduction of routine vaccination with Pneumococcal Conjugate Vaccine (PCV7). Eur J Pediatr 2010; 169:1123. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. Yu J, Salamon D, Marcon M, Nahm MH. Pneumococcal serotypes causing pneumonia with pleural effusion in pediatric patients. J Clin Microbiol 2011; 49:534. Thomas MF, Sheppard CL, Guiver M, et al. Emergence of pneumococcal 19A empyema in UK children. Arch Dis Child 2012; 97:1070. Kaplan SL, Barson WJ, Lin PL, et al. Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2013; 32:203. Antachopoulos C, Tsolia MN, Tzanakaki G, et al. Parapneumonic pleural effusions caused by Streptococcus pneumoniae serotype 3 in children immunized with 13-valent conjugated pneumococcal vaccine. Pediatr Infect Dis J 2014; 33:81. Tan TQ, Mason EO Jr, Barson WJ, et al. Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae. Pediatrics 1998; 102:1369. Wexler ID, Knoll S, Picard E, et al. Clinical characteristics and outcome of complicated pneumococcal pneumonia in a pediatric population. Pediatr Pulmonol 2006; 41:726. Byington CL, Spencer LY, Johnson TA, et al. An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations. Clin Infect Dis 2002; 34:434. Ramphul N, Eastham KM, Freeman R, et al. Cavitatory lung disease complicating empyema in children. Pediatr Pulmonol 2006; 41:750. Bender JM, Ampofo K, Korgenski K, et al. Pneumococcal necrotizing pneumonia in Utah: does serotype matter? Clin Infect Dis 2008; 46:1346. Waters AM, Kerecuk L, Luk D, et al. Hemolytic uremic syndrome associated with invasive pneumococcal disease: the United kingdom experience. J Pediatr 2007; 151:140. Bender JM, Ampofo K, Byington CL, et al. Epidemiology of Streptococcus pneumoniae-induced hemolytic uremic syndrome in Utah children. Pediatr Infect Dis J 2010; 29:712. Song JY, Nahm MH, Cheong HJ, Kim WJ. Impact of preceding flu-like illness on the serotype distribution of pneumococcal pneumonia. PLoS One 2014; 9:e93477. García-García ML, Calvo C, Pozo F, et al. Spectrum of respiratory viruses in children with communityacquired pneumonia. Pediatr Infect Dis J 2012; 31:808. Woods CR, Bryant KA. Viral infections in children with community-acquired pneumonia. Curr Infect Dis Rep 2013; 15:177. Byington CL, Korgenski K, Daly J, et al. Impact of the pneumococcal conjugate vaccine on pneumococcal parapneumonic empyema. Pediatr Infect Dis J 2006; 25:250. Grijalva CG, Nuorti JP, Zhu Y, Griffin MR. Increasing incidence of empyema complicating childhood community-acquired pneumonia in the United States. Clin Infect Dis 2010; 50:805. Hardie WD, Roberts NE, Reising SF, Christie CD. Complicated parapneumonic effusions in children caused by penicillin-nonsusceptible Streptococcus pneumoniae. Pediatrics 1998; 101:388. Iroh Tam PY, Coombes B, Madoff L, Pelton SI. Severity of invasive pneumococcal disease in children caused by susceptible and nonsusceptible isolates. Pediatr Infect Dis J 2014; 33:1206. Marrie TJ. Community-acquired pneumonia. Clin Infect Dis 1994; 18:501. Le Monnier A, Carbonnelle E, Zahar JR, et al. Microbiological diagnosis of empyema in children: comparative evaluations by culture, polymerase chain reaction, and pneumococcal antigen detection in pleural fluids. Clin Infect Dis 2006; 42:1135. Resti M, Moriondo M, Cortimiglia M, et al. Community‐acquired bacteremic pneumococcal pneumonia in children: diagnosis and serotyping by real‐time polymerase chain reaction using blood samples. Clin Infect Dis 2010; 51:1042. Azzari C, Moriondo M, Indolfi G, et al. Realtime PCR is more sensitive than multiplex PCR for diagnosis and serotyping in children with culture negative pneumococcal invasive disease. PLoS One 2010; 5:e9282. Ramirez M, Melo-Cristino J. Expanding the diagnosis of pediatric bacteremic pneumococcal pneumonia from blood cultures to molecular methods: advantages and caveats. Clin Infect Dis 2010; 51:1050. Avni T, Mansur N, Leibovici L, Paul M. PCR using blood for diagnosis of invasive pneumococcal disease: systematic review and meta-analysis. J Clin Microbiol 2010; 48:489. Rein MF, Gwaltney JM Jr, O'Brien WM, et al. Accuracy of Gram's stain in identifying pneumococci in sputum. JAMA 1978; 239:2671. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis 2011; 53:e25. Chumpa A, Bachur RG, Harper MB. Bacteremia-associated pneumococcal pneumonia and the benefit of initial parenteral antimicrobial therapy. Pediatr Infect Dis J 1999; 18:1081. Choi EH, Lee HJ. Clinical outcome of invasive infections by penicillin-resistant Streptococcus pneumoniae in Korean children. Clin Infect Dis 1998; 26:1346. Deeks SL, Palacio R, Ruvinsky R, et al. Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae. The Streptococcus pneumoniae Working Group. Pediatrics 1999; 103:409. Cardoso MR, Nascimento-Carvalho CM, Ferrero F, et al. Penicillin-resistant pneumococcus and risk of treatment failure in pneumonia. Arch Dis Child 2008; 93:221. Clifford V, Tebruegge M, Vandeleur M, Curtis N. Question 3: can pneumonia caused by penicillin-resistant Streptococcus pneumoniae be treated with penicillin? Arch Dis Child 2010; 95:73. Friedland IR. Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillinsusceptible pneumococcal disease. Pediatr Infect Dis J 1995; 14:885. Pírez MC, Martínez O, Ferrari AM, et al. Standard case management of pneumonia in hospitalized children in Uruguay, 1997 to 1998. Pediatr Infect Dis J 2001; 20:283. Kaplan SL, Barson WJ, Lin PL, et al. Continued decline in invasive pneumococcal infections in children among 8 children's hospitals in the United States 2011 to 2013. https://idsa.confex.com/idsa/2014/webprogram/Paper45148.html (Accessed on November 17, 2014). Centers for Disease Control and Prevention. ABCs Report: Streptococcus pneumoniae, 2013. www.cdc.gov/abcs/reports-findings/survreports/spneu13.html (Accessed on November 17, 2014). Pelton SI, Huot H, Finkelstein JA, et al. Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J 2007; 26:468. Moore MR, Gertz RE Jr, Woodbury RL, et al. Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005. J Infect Dis 2008; 197:1016. Bradley JS, Arguedas A, Blumer JL, et al. Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia. Pediatr Infect Dis J 2007; 26:868. Feikin DR, Schuchat A, Kolczak M, et al. Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997. Am J Public Health 2000; 90:223.